Somatic Arc protein expression in hippocampal granule cells is increased in response to environmental change but independent of task-specific learning.

Activated neurons express immediate-early genes, such as Arc. Expression of Arc in the hippocampal granule cell layer, an area crucial for spatial learning and memory, is increased during acquisition of spatial learning; however, it is unclear whether this effect is related to the task-specific learning process or to nonspecific aspects of the testing procedure (e.g. exposure to the testing apparatus and exploration of the environment). Herein, we show that Arc-positive cells numbers are increased to the same extent in the granule cell layer after both acquisition of a single spatial learning event in the active place avoidance task and exploration of the testing environment, as compared to naïve (i.e. caged) mice. Repeated exposure the testing apparatus and environment did not reduce Arc expression. Furthermore, Arc expression did not correlate with performance in both adult and aged animals, suggesting that exploration of the testing environment, rather than the specific acquisition of the active place avoidance task, induces Arc expression in the dentate granule cell layer. These findings thus suggest that Arc is an experience-induced immediate-early gene.

Investigation into the mechanisms by which nedocromil sodium, frusemide and bumetanide inhibit the histamine-induced itch and flare response in human skin in vivo.

BACKGROUND: In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine-induced itch and flare. In asthma, the Na+/K+/2Cl- cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium. OBJECTIVE: To compare the effects of these drugs in the histamine-induced itch, flare and weal response in human skin in vivo and elucidate their site of action. METHODS: Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single-blind studies. In study 1, histamine (20 microL of 100 microM) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min. RESULTS: In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P<0.05). Weal areas and blood flux in the flare were unaffected. In study 2, itch scores, flare areas and weal areas were not inhibited. Also, blood flux values in areas of drug and water iontophoresis were not different. CONCLUSION: This study has provided evidence to support the hypothesis that nedocromil sodium, frusemide and bumetanide inhibit sensory nerve activation to reduce the itch and flare responses induced by histamine in human skin in vivo. It is likely that inhibition of a Na+/K+/2Cl- cotransporter in the sensory nerve membrane is a possible mechanism of action.